Costs related to care of patients who undergo lobectomy for lung cancer may vary depending on patient, disease, and treating facility characteristics. We aimed to identify underlying case mix factors that contribute to variability of 90-day costs of lobectomy for early-stage lung cancer. The Society of Thoracic Surgeons General Thoracic Surgery Database was queried for lobectomy for clinical stage I lung cancer (2008-2013). Demographics, clinical outcomes, and 90-day episode-of-care costs across all care settings were analyzed for patients successfully linked to Medicare data. Hospital costs were estimated from charges using cost-to-charge ratios. Comprehensive regression models were created to identify impact of preoperative patient factors and hospital characteristics on costs, and to delineate additive costs due to perioperative outcomes and complications. The mean 90-day cost for lobectomy was $45,080 ± $38,239. Variables associated with significant additive costs were age greater than or equal to 75 years, American Society of Anesthesiologists classification III or IV, forced expiratory volume in 1 second less than 80% predicted, body mass index less than 18.5 or greater than 35, current or past smoker, cerebrovascular disease, chronic kidney disease, impaired functional status, open thoracotomy, prolonged operative time, government hospitals, metropolitan setting, and geographic location. Patients with 1 or more postoperative complication resulted in an overall mean added cost of $27,259. Added costs increased with the number of complications; isolated recurrent laryngeal nerve paresis ($3,911) and respiratory failure ($35,011) were associated with the least and most additive cost, respectively. Lobectomy is associated with substantial variability of episode-of-care costs. Variability is driven by patient demographic and clinical factors, hospital characteristics, and the occurrence and severity of complications.